The cytotoxic activity of human monocytes towards anti-D-sensitized Rh(D)-positive red cells in vitro was studied in relation to the age and sex of healthy monocyte donors. It was found that cytotoxic activity of monocytes from young females (age range 18-40 years) was significantly less than that of monocytes from age-matched males, irrespective of the use of oral contraceptives. No such difference was found between monocytes from older males and females (age range 43-63 years). The cytotoxic activity of monocytes from the two latter groups of donors was similar to that of young males. In the presence of cytochalasin B, which enhances the cytotoxic activity of monocytes, no male-female difference was detected, indicating that the maximal cytotoxic capacity of monocytes from young females is similar to that of monocytes from young males. We have previously presented evidence that the cytotoxic activity of monocytes is mediated by lysosomal enzymes released by these cells. These present data suggest that the reduction in cytotoxic activity of monocytes from young females might be a result of a reduced lysosomal enzyme release which is possibly related to the in vivo action of female sex hormones. However, we were not able to detect an inhibitory effect of oestrogens and progestagens on cytotoxic activity of monocytes from males in vitro.